AB0390 OVERACTIVATION OF THE RENIN ANGIOTENSIN SYSTEM AS A POSSIBLE CONTRIBUTOR TO THE INCREASED CARDIOVASCULAR RISK IN RHEUMATOID ARTHRITIS (RA); EVALUATION OF LEUKOCYTE EXPRESSION OF ANGIOTENSIN II RECEPTOR TYPE 1 AND TYPE 2 IN A POPULATION OF RA PATIENTS.
Authors: C. Bentivenga, N. E. Politi, A. Bragagni, E. R. Cosentino, F. A. G. Cicero, M. Reta, C. Borghi
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> rheumatoid arthritis (RA) is a chronic systemic autoinflammatory disease of unknown aetiology characterized by joint inflammation and multiple comorbidities, with a prevalence of approximately 1% of the adult population. It is considered an independent cardiovascular (CV) risk factor, in fact it is associated with significantly increased CV morbidity and mortality. The renin angiotensin system (RAS) is a hormonal cascade with pleiotropic effects. Not only is it crucial in blood pressure regulation but it also plays an important role, among many other effects, in inflammation. High circulating levels of proinflammatory cytokines such as TNF-α and IL-6 are critical in the pathogenesis of RA as well as in determining increased CV morbidity and mortality among these patients. TNF-α and IL-6 activate the systemic and local RAS; in turn, Angiotensin II (Ang II) increases several proinflammatory cytokines among which TNF-α and IL-6. Therefore, a self-perpetuating vicious circle between RAS and cytokines is triggered. Activation of the classical RAS leads to Angiotensin II (Ang II) formation which binds to Ang II receptors type 1 (AT1R) and 2 (AT2R). RAS overactivation is essential in determining vascular inflammation and endothelial dysfunction through its proinflammatory and profibrotic effects. <h3>Objectives</h3> to determine whether RAS activity is higher among RA patients. <h3>Methods</h3> leukocyte AT1R and AT2R mRNA was extracted and measured by real-time polymerase chain reaction analysis (RT-PCR) from 18 RA patients with stable disease and no traditional CV risk factors (mean age 52.17±11.4) and 10 healthy controls (mean age 43.8±8.61). Intergroup comparisons were made using the Mann-Whitney U test. <h3>Results</h3> A significantly higher expression of AT1R was found in RA patients compared to healthy controls (p&lt;0.01). Even though the finding did not reach statistical significance, AT2R expression was also higher in RA patients (p =0.072). <h3>Conclusion</h3> the results suggest AT1R and possibly AT2R upregulation in RA patients, indicating that RAS overactivation could contribute to the increased CV risk observed in RA patients. If such findings are confirmed by further research, they could have important implications in terms of prevention and treatment strategies for RA patients as RA is associated with an elevated CV risk that is often overlooked and underdiagnosed in these populations. <h3>References</h3> [1]Moreira FRC, de Oliveira TA, Ramos NE, Abreu MAD, Simões E Silva AC. The role of renin angiotensin system in the pathophysiology of rheumatoid arthritis. <i>Mol Biol Rep</i>. 2021;48(9):6619-6629. doi:10.1007/s11033-021-06672-8 [2]Chang Y, Wei W. Angiotensin II in inflammation, immunity and rheumatoid arthritis. <i>Clin Exp Immunol</i>. 2015;179(2):137-145. doi:10.1111/cei.12467 [3]Hansildaar R, Vedder D, Baniaamam M, Tausche AK, Gerritsen M, Nurmohamed MT. Cardiovascular risk in inflammatory arthritis: rheumatoid arthritis and gout. <i>Lancet Rheumatol</i>. 2021;3(1):e58-e70. doi:10.1016/S2665-9913(20)30221-6 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.